Chemical magic transforms skin cells into nerve cells

Small-molecule drugs provide simpler alternative to genes delivered by viruses

CHEMICAL COCKTAIL  Adult skin cells begin to transform into neurons (blue circles with colorful tendrils) just a week after being dosed with seven small-molecule drugs.

Courtesy of Gang Pei and Jian Zhao 

In a feat of biological wizardry worthy of Harry Potter, scientists have transformed skin cells into nerve cells — no magic wand required.

Just a handful of chemicals can conjure up nerve cells that look and act like the real thing, Chinese researchers report August 6 in two studies in Cell Stem Cell. Even skin cells from Alzheimer’s patients can morph into seemingly healthy neurons, one of the new studies showed. The other reported a similar feat using mouse cells. Scientists have transformed skin cells into nerve cells before, but not as simply.

“I think it’s a big deal,” says Stanford University stem cell biologist Marius Wernig. “I was surprised that it was actually possible.” If the chemical technique, which uses small-molecule drugs, can change skin cells into something as dramatically different as nerve cells, Wernig says, scientists could potentially concoct any type of cell in the body.

One day, scientists may even be able to package a few chemicals in a pill and give it to brain-damaged patients to replace busted neurons, says Gang Pei, acoauthor of the human study, and a cell biologist from the Chinese Academy of Sciences and Tongji University in Shanghai.

“That’s the dream scenario,” he says.

Scientists have spent years working on ways to use human cells in therapies for injuries and diseases. Healthy cells transplanted into patients could potentially repair tissue damaged in strokes or heart attacks or be used to treat Alzheimer’s disease or diabetes. Finding good sources of cells isn’t easy, though. Embryonic cells are adaptable, but research on them raises ethical issues. And adult cells aren’t nearly as versatile.

Still, in the last decade scientists have had some success. Dosing adult cells with a genetic cocktail forces them to crank out proteins called transcription factors. These proteins snap cells back to an embryonic-like state. Scientists can then reprogram the cells into new ones. In 2010, using the gene-based method, Wernig and colleagues figured out how to convert mouse skin cells directly into nerve cells (SN: 2/27/10, p. 5).

The method has some drawbacks, though. Scientists use viruses to sneak genes into cells’ DNA, but no one knows exactly where the genes will squeeze in. These extra bits of DNA could muck up important parts of the cells’ genetic instruction book. What’s more, Wernig says, “people are very worried that these viruses could be reactivated.” The fear is that patients receiving cell transplants could potentially end up with a dangerous batch of cells.

“People have been searching for ways to reprogram cells without using transcription factors,” says neurobiologist Philipp Koch of the University of Bonn in Germany. In recent years, scientists have swapped out transcription factors for small-molecule drugs, and have used these drugs to convert adult cells into stem cells (SN Online: 7/18/13). But until now, no one had used the method to make nerve cells directly from skin.

Pei and colleagues added a mixture of seven drugs to human skin cells collected from healthy people and Alzheimer’s patients. Just seven days later, about 20 percent of the cells began to turn into nerve cells, or neurons. They started sprouting characteristic branching tendrils and even developed the ability to send electrical signals.  

The work is proof-of-concept, Pei says, but researchers could theoretically transplant neurons made from a patients’ own skin cells into the body or use the neurons to test new therapies in the lab. Doctors could then offer a more personalized treatment approach, where patients use the therapy that worked best on their cells, instead of trying out different therapies themselves.

Wernig says the findings are convincing, but he’d like to understand how exactly the chemicals perform their biological alchemy. The authors, he says, “still have no idea how this happens.”

Meghan Rosen is a staff writer who reports on the life sciences for Science News. She earned a Ph.D. in biochemistry and molecular biology with an emphasis in biotechnology from the University of California, Davis, and later graduated from the science communication program at UC Santa Cruz.

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